This Program Project application "The Role of mRNA Decay in the Immune System" is designed to coordinate the efforts of investigators who have been studying post-transcriptional regulation, in particular, the mechanisms involved in mRNA turnover. The program is to be directed by Sidney Pestka, chair of the Department of Molecular Genetics, Microbiology and Immunology and an investigator with a long term interest in interferons, cytokines, signal transduction and mRNA turnover. The Program Project consists of five projects: 1. Adherence Activated Monocyte Genes; 2. ARE & non-ARE Pathways Regulating CD154 mRNA Stability; 3. Translational Regulation by the TNF Alpha AU-rich Element; 4. Regulation of Cytokine Gene Expression by mRNA Turnover; 5: Regulation of RANKL Expression in T-Lymphocytes. Four of the individuals have experience in the study of mRNA lifetime; two of the investigators are immunologists. The Program Project contains an administrative core and six small cores to make the work efficient and effective. The cores are: A) Flow Cytometry Facility; B) Real-Time PCR Facility; C) Imaging Facility; D) Irradiation Facility; E) DNA Synthesis & Sequencing Facility; F) Real time Fluorescence Resonance Energy Facility. The overall aim of this application is to understand how mRNA turnover controls various steps in immune activation and differentiation during immune responses. One of the fast methods to control changes in protein expression is by modification of the rate of mRNA decay, a post-transcriptional process. Understanding the role of mRNA turnover in regulation of the immune system will provide an opportunity to develop new therapeutics to control these processes and treat a variety of diseases such as rheumatoid arthritis and other immune disorders.